Emerging designs in orthopaedics: expertise-based randomized controlled trials.
In this article, we discuss the limitations of conventional randomized controlled trials (RCTs) in the surgical field. Surgeons are often believers in certain surgical techniques and therefore can be reluctant to learn new interventions. In expertise-based trials, the patients are randomized to surgeons with expertise in the intervention under investigation. In conventional RCTs, patients are randomized to an intervention, and surgeons will perform this intervention regardless of whether this is the surgery they typically undertake. Conventional randomization may lead to surgery performed by a less experienced or less motivated surgeon, resulting in differential expertise bias. Expertise-based trials can overcome these limitations if potential pitfalls are taken into account.


Insulin resistance and diabetic macular oedema in type 2 diabetes mellitus.
To evaluate the association between insulin resistance and diabetic macular oedema in type 2 diabetes. Patients with type 2 diabetes who agreed to undergo blood sampling were enrolled into this cross-sectional study. Patients who had received treatment for macular oedema within the past 3 months and those with other retinal diseases were excluded. The following data were recorded: age, sex, time of diabetes evolution, HbA1c, ophthalmologic and systemic treatment, and lens status. Optical coherence tomography (OCT) was performed to determine the morphological patterns of macular oedema. Insulin resistance was established by a McAuley index of <6.3 and fasting insulin levels of >16 mU/l. A total of 177 eyes from 90 patients were included; 27.1% of eyes were from insulin-resistant patients. There were no differences in age, time of evolution, sex, HbA1c level or lens status between insulin-resistant and non-resistant patients. Insulin-resistant patients were more likely to have exogenous insulin therapy (p<0.05; OR=3.8). An association was found between diabetic cystoid macular oedema and insulin resistance (Fisher exact test p=0.007; OR=2.53, 95% CI 1.52 to 4.2). There were no associations between insulin resistance and the other morphological patterns of oedema. Patients undergoing insulin therapy were found to have an association with a diffuse retinal thickening pattern on OCT (p=0.036; OR=1.4). However, no association was found between insulin therapy and the presence of cystoid macular oedema. The findings of this study indicate a relationship between insulin resistance and cystoid macular oedema that unrelated to the use of insulin. Insulin treatment was associated with diffuse macular oedema.


Optimization of human papillomavirus type 16 (HPV-16) L1 expression in plants: comparison of the suitability of different HPV-16 L1 gene variants and different cell-compartment localization.
Virus-like particle-based vaccines for high-risk human papillomaviruses (HPVs) appear to have great promise; however, cell culture-derived vaccines will probably be very expensive. The optimization of expression of different codon-optimized versions of the HPV-16 L1 capsid protein gene in plants has been explored by means of transient expression from a novel suite of Agrobacterium tumefaciens binary expression vectors, which allow targeting of recombinant protein to the cytoplasm, endoplasmic reticulum (ER) or chloroplasts. A gene resynthesized to reflect human codon usage expresses better than the native gene, which expresses better than a plant-optimized gene. Moreover, chloroplast localization allows significantly higher levels of accumulation of L1 protein than does cytoplasmic localization, whilst ER retention was least successful. High levels of L1 (>17% total soluble protein) could be produced via transient expression: the protein assembled into higher-order structures visible by electron microscopy, and a concentrated extract was highly immunogenic in mice after subcutaneous injection and elicited high-titre neutralizing antibodies. Transgenic tobacco plants expressing a human codon-optimized gene linked to a chloroplast-targeting signal expressed L1 at levels up to 11% of the total soluble protein. These are the highest levels of HPV L1 expression reported for plants: these results, and the excellent immunogenicity of the product, significantly improve the prospects of making a conventional HPV vaccine by this means.


Proteomic Profile of Mouse Brain Aging Contributions to Mitochondrial Dysfunction, DNA Oxidative Damage, Loss of Neurotrophic Factor, and Synaptic and Ribosomal Proteins.
The deleterious effects of aging on the brain remain to be fully elucidated. In the present study, proteomic changes of young (4-month) and aged (16-month) B6129SF2/J male mouse hippocampus and cerebral cortex were investigated by using nano liquid chromatography tandem mass spectrometry (NanoLC-ESI-MS/MS) combined with tandem mass tag (TMT) labeling technology. Compared with the young animals, 390 hippocampal proteins (121 increased and 269 decreased) and 258 cortical proteins (149 increased and 109 decreased) changed significantly in the aged mouse. Bioinformatic analysis indicated that these proteins are mainly involved in mitochondrial functions (FIS1, DRP1), oxidative stress (PRDX6, GSTP1, and GSTM1), synapses (SYT12, GLUR2), ribosome (RPL4, RPS3), cytoskeletal integrity, transcriptional regulation, and GTPase function. The mitochondrial fission-related proteins FIS1 and DRP1 were significantly increased in the hippocampus and cerebral cortex of the aged mice. Further results in the hippocampus showed that ATP content was significantly reduced in aged mice. A neurotrophin brain-derived neurotrophic factor (BNDF), a protein closely related with synaptic plasticity and memory, was also significantly decreased in the hippocampus of the aged mice, with the tendency of synaptic protein markers including complexin-2, synaptophysin, GLUR2, PSD95, NMDAR2A, and NMDAR1. More interestingly, 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA oxidative damage, increased as shown by immunofluorescence staining. In summary, we demonstrated that aging is associated with systemic changes involving mitochondrial dysfunction, energy reduction, oxidative stress, loss of neurotrophic factor, synaptic proteins, and ribosomal proteins, as well as molecular deficits involved in various physiological/pathological processes.


Evaluation of the Family Integrated Care model of neonatal intensive care: a cluster randomized controlled trial in Canada and Australia.
Admission to the neonatal intensive care unit (NICU) may disrupt parent-infant interaction with adverse consequences for infants and their families. Several family-centered care programs promote parent-infant interaction in the NICU; however, all of these retain the premise that health-care professionals should provide most of the infant's care. Parents play a mainly supportive role in the NICU and continue to feel anxious and unprepared to care for their infant after discharge. In the Family Integrated Care (FICare) model, parents provide all except the most advanced medical care for their infants with support from the medical team. Our hypothesis is that infants whose families complete the FICare program will have greater weight gain and better clinical and parental outcomes compared with infants provided with standard NICU care. FICare is being evaluated in a cluster randomized controlled trial among infants born at ≤ 33 weeks' gestation admitted to 19 Canadian, 6 Australian, and 1 New Zealand tertiary-level NICU. Trial enrollment began in April, 2013, with a target sample size of 675 infants in each arm, to be completed by August, 2015. Participating sites were stratified by country, and by NICU size within Canada, for randomization to either the FICare intervention or control arm. In intervention sites, parents are taught how to provide most of their infant's care and supported by nursing staff, veteran parents, a program coordinator, and education sessions. In control sites standard NICU care is provided. The primary outcome is infants' weight gain at 21 days after enrollment, which will be compared between the FICare and control groups using Student's t-test adjusted for site-level clustering, and multi-level hierarchical models accounting for both clustering and potential confounders. Similar analyses will examine secondary outcomes including breastfeeding, clinical outcomes, safety, parental stress and anxiety, and resource use. The trial was designed, is being conducted, and will be reported according to the CONSORT 2010 guidelines for cluster randomized controlled trials. By evaluating the impact of integrating parents into the care of their infant in the NICU, this trial may transform the delivery of neonatal care. NCT01852695 , registered December 19, 2012.


Sowa Rigpa Humanitarianism: Local Logics of Care within a Global Politics of Compassion.
This article examines the circulation of humanitarian ideas, materials, and actions in a non-biomedical and non-Judeo-Christian context: Sowa Rigpa or Tibetan medical camps in India and Nepal. Through these camps, practitioners and patients alike often overtly articulate Sowa Rigpa medicine as part of a broader humanitarian "good" motivated by a Buddhist-inflected ethics of compassion and a moral economy of care, diverging from mainstream public health and conventional humanitarian projects. Three ethnographic case studies demonstrate how micro-political interactions at camps engage with ethical and religious imaginaries. We show how the ordinary ethics of Sowa Rigpa humanitarianism gain distinct political meaning in contrast to non-Tibetan forms of aid, reconfiguring the relationship between Buddhism, essential medicines, moral economies, and politics. While Sowa Rigpa as a medical system operates transnationally, these camps are organized around local logics of emergent care, employing narratives of "charity" and Buddhist compassion when addressing health needs.


[Public laboratories for vaccine production: a new paradigm].
In Latin America and the Caribbean, public laboratories that produce vaccines have contributed in varying degrees to the control and eradication of vaccine-preventable diseases, and several of them are manufacturing vaccines that are routinely applied in national immunization programs, such as the vaccine against tuberculosis (made with the bacillus of Calmette-Guérin, BCG), the triple vaccine against diphtheriatetanus-pertussis (DTP), tetanus toxoid (TT), the vaccine against measles and the oral vaccine against polio. Thanks to recent scientific strides, one can foresee an important increase in the number of safe and effective vaccines that will be available in the near future for use in routine vaccination programs. However, there are high costs involved in developing such vaccines and in protecting the intellectual property rights involved, and few laboratories in Latin America have the technical capacity to research and develop these vaccines. Such factors will affect the speed with which they are assimilated into vaccination programs in countries of the Region. Currently, public laboratories that manufacture vaccines in the Region are not equipped to compete in this new scenario and run the risk of being completely outmarketed. Thus, they must radically change their style of management and their scientific and technical capabilities, backed by a commitment from governments to improve and strengthen those political and financial aspects that can assure that national laboratories participate in the sustainable supply of vaccines to immunization programs, as well as in researching, developing, and producing new vaccines.


Wearable electroencephalography. What is it, why is it needed, and what does it entail?
The electroencephalogram (EEG) is a classic noninvasive method for measuring a person's brain waves and is used in a large number of fields: from epilepsy and sleep disorder diagnosis to brain-computer interfaces (BCIs). Electrodes are placed on the scalp to detect the microvolt-sized signals that result from synchronized neuronal activity within the brain. Current long-term EEG monitoring is generally either carried out as an inpatient in combination with video recording and long cables to an amplifier and recording unit or is ambulatory. In the latter, the EEG recorder is portable but bulky, and in principle, the subject can go about their normal daily life during the recording. In practice, however, this is rarely the case. It is quite common for people undergoing ambulatory EEG monitoring to take time off work and stay at home rather than be seen in public with such a device. Wearable EEG is envisioned as the evolution of ambulatory EEG units from the bulky, limited lifetime devices available today to small devices present only on the head that can record EEG for days, weeks, or months at a time. Such miniaturized units could enable prolonged monitoring of chronic conditions such as epilepsy and greatly improve the end-user acceptance of BCI systems. In this article, we aim to provide a review and overview of wearable EEG technology, answering the questions: What is it, why is it needed, and what does it entail? We first investigate the requirements of portable EEG systems and then link these to the core applications of wearable EEG technology: epilepsy diagnosis, sleep disorder diagnosis, and BCIs. As a part of our review, we asked 21 neurologists (as a key user group) for their views on wearable EEG. This group highlighted that wearable EEG will be an essential future tool. Our descriptions here will focus mainly on epilepsy and the medical applications of wearable EEG, as this is the historical background of the EEG, our area of expertise, and a core motivating area in itself, but we will also discuss the other application areas. We continue by considering the forthcoming research challenges, principally new electrode technology and lower power electronics, and we outline our approach for dealing with the electronic power issues. We believe that the optimal approach to realizing wearable EEG technology is not to optimize any one part but to find the best set of tradeoffs at both the system and implementation level. In this article, we discuss two of these tradeoffs in detail: investigating the online compression of EEG data to reduce the system power consumption and the optimal method for providing this data compression.


Effect of administration of Sar1-Ala8-angiotensin II during the development and maintenance of renal hypertension in the rat.
1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.


Films of lutetium bisphthalocyanine nanowires as electrochemical sensors.
Lutetium bisphthalocyanine (LuPc(2)) nanowires have been successfully obtained by electrophoretic deposition (EPD). The influence of the deposition conditions and annealing in the structure of the films has been studied by AFM, SEM, X-ray diffraction (XRD), UV-vis absorption, and near-infrared (NIR). The electrochemical properties of the EDP films immersed in different electrolytic solutions (KCl, MgCl(2), KClO(4), HCl, and NaOH) indicate that anions diffuse inside the film to maintain the electroneutrality and the kinetics follows the Randles-Sevcik equation. The stability of the response increases strongly upon annealing due to the improvement of the adhesion of the sensitive material to the substrate. The EPD films have been successfully used to detect caffeic acid (an antioxidant of interest in the food industry). The anodic peak associated with the oxidation of caffeic acid appears at 0.54 V and is linearly dependent on the caffeic acid concentration in the 6 × 10(-5) M to 5 × 10(-4) M range with a detection limit of 3.12 × 10(-5) M. The electrochemical behavior of the annealed LuPc(2) EPD films is similar to that observed using Langmuir-Blodgett (LB) nanostructured films. However, the different molecular organization of the molecules inside the film causes differences in the shape and position of the peaks. Although LuPc(2) sensors prepared with both EPD and LB techniques provide stable and reproducible responses, the use of EPD is preferred for real sensing applications because of its lower cost, shorter preparation time, and longer lifetime.


Uniformly embedded metal oxide nanoparticles in vertically aligned carbon nanotube forests as pseudocapacitor electrodes for enhanced energy storage.
Carbon nanotube (CNT) forests were grown directly on a silicon substrate using a Fe/Al/Mo stacking layer which functioned as both the catalyst material and subsequently a conductive current collecting layer in pseudocapacitor applications. A vacuum-assisted, in situ electrodeposition process has been used to achieve the three-dimensional functionalization of CNT forests with inserted nickel nanoparticles as pseudocapacitor electrodes. Experimental results have shown the measured specific capacitance of 1.26 F/cm(3), which is 5.7 times higher than pure CNT forest samples, and the oxidized nickel nanoparticle/CNT supercapacitor retained 94.2% of its initial capacitance after 10,000 cyclic voltammetry tests.


Permanent jejunal fistula: promising method for obtaining small intestinal chyme without disturbing intestinal function.
Accurate information on changes in small intestinal microflora in dogs is rather limited because of difficulties in obtaining samples of small intestinal chyme. In the study reported here, intussuscepted nipple valves were surgically placed into the jejunum of seven laboratory beagles to obtain intestinal juice samples. The influence of the fistula on intestinal motility was determined by use of barium-impregnated polyethylene spheres (BIPS) and on microflora by use of bacterial culturing. The BIPS were fed two weeks before surgery and again five weeks after surgery. Bacterial samples were collected before (fecal samples), during (small intestinal samples) and 11 weeks after surgery. There were no surgical complications, and the animals tolerated the fistula well. Mean orocolic transit percentage was 93% before and 83% after surgery, and notable changes in gastrointestinal motility were not seen, except in one dog. The surgery did not markedly alter the bacterial flora in feces. Microflora did change in small intestinal samples; however, methodologic factors may explain most of these differences. In conclusion, the nipple valve is a promising method that creates easy and safe long-term access to the jejunum and appears not to have an influence on intestinal function.


Association of Diaphragm Contractility and Postural Control in a Chronic Ankle Instability Population: A Preliminary Study.
Altered reorganization of the sensorimotor system after an initial lateral ankle sprain may lead to a chronic neuromuscular maladaptation in multiple body locations. Specifically, decreased diaphragm contractility has been observed in patients with chronic ankle instability (CAI). The diaphragm has an essential role in postural control. Decreased diaphragm contractility could associate with diminished postural control commonly observed in patients with CAI. However, no study has determined if diaphragm contractility contributes to postural control in a CAI population. Decreased diaphragm contractility would be negatively associated with static postural control in patients with CAI. Cross-sectional study design. Level 4. A total of 15 participants with CAI participated voluntarily. An ultrasonography assessment was performed to quantify the right and left hemidiaphragm thickness at the end of resting inspiration and expiration in supine while breathing quietly. The degree of diaphragm contractility was calculated from the diaphragm thickness. Participants performed 3 eyes-open trials of a 20-second single-leg balance task on the involved limb. Static postural control measures included the center of pressure velocity (COPV) and mean of time-to-boundary (TTB) minima in the anteroposterior (AP) and mediolateral directions. Moderate correlations of the right hemidiaphragm contractility were observed with COPV (ρ = -0.54) and TTB mean minima (ρ = 0.56) (P < 0.05) in the AP direction. The left hemidiaphragm contractility was moderately correlated with COPV (ρ = -0.56) and TTB mean minima (ρ = 0.60) (P < 0.05) in the AP direction. Lower diaphragm contractility may be associated with diminished static postural control in the AP direction in patients with CAI. This study highlights diaphragm contractility could be a potential connection with diminished static postural control in patients with CAI. Our data raise new avenues for future exploration including potential beneficial effects of implementation of diaphragm breathing exercises and techniques for restoring static postural control in patients with CAI.


Behavioural and physiological consequences of acute social defeat in growing gilts: effects of the social environment.
Endocrine, behavioural and immunologic processes, together with body growth, were evaluated in gilts that were defeated at 10 weeks of age in resident-intruder tests. Immediately after defeat, gilts were either separated from or reunited with a familiar conspecific (litter-mate; always a barrow). Gilts were assigned to one of four treatments: (a) DI: defeat, followed by isolation (separation from original litter-mate; n=8); (b) I: no defeat, isolation (control group; n=9); (c) DP; defeat, followed by pair-housing (reunion with original litter-mate; n=8); and (d) P: no defeat, pair-housing (control group; n=8). The following general conclusions were derived: (1) social defeat caused pronounced short-term elevations in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary activities, and of prolactin levels. Moreover, as soon as 1h after defeat, percentages of blood lymphocytes and neutrophilic granulocytes were, respectively, decreased and increased; (2) social defeat had some long-lasting influence on behaviour and physiology, but isolation predominantly determined responses in the longer term. Defeat, as well as isolation, resulted in increased cardiovascular activities compared to P controls, as observed in a novel object test (NOT: +7 days) and an aversion test (AVT: +14 days). Moreover, defeated as well as isolated gilts did not habituate to a repeated novel environment test (NET: -7, +2 and +7 days) in terms of frequencies of vocalising, whereas P controls did. Isolation, through the separation from any other pig, was responsible for the other observed long-term characteristics, which developed progressively. Isolated gilts showed high mobilities and high cortisol responses in the repeated NET (+7 days), not being habituated. This contrasted the reactions of pair-housed gilts, which were much reduced. In addition to their high cardiovascular activities in the NOT and the AVT, isolated gilts also displayed higher heart rates in the repeated NET and during human presence following the NOT, compared to pair-housed gilts. Finally, isolated gilts were more inhibited to approach a novel object (in the NOT) than pair-housed pigs; and (3) stress responses of defeated gilts were modulated by the subsequent social environment. Stimulation of the HPA-axis (plasma- and salivary cortisol) was prolonged in those defeated gilts which were isolated (observed in the first hour). Changes in leucocyte subsets were still observed after 3 days in DI, but were 'normalised' within 1 day in DP gilts. Two days after defeat, habituation to the repeated NET in terms of mobility and salivary cortisol responses occurred in control and DP gilts, but not in DI gilts. We argue that these effects of the social environment shortly after defeat were related to a stress-reducing effect of a stable social relationship, i.e. social support.


Human CD2 is functional in CD2 transgenic mice.
We aimed to study the biochemical consequences of T-cell activation via the CD2 antigen in mouse T cells. The lack of stimulatory monoclonal antibodies against the mouse CD2 antigen led us to analyse this problem in transgenic mice carrying and expressing the human CD2 gene. Monoclonal antibodies to the human CD2 antigen that were mitogenic for human T cells induced proliferation of mouse T cells from the CD2 transgenic mice. Stimulation was accompanied by rapid phosphorylation of the murine CD3 gamma chain and T-cell receptor zeta chain. These results demonstrate that the human CD2 antigen is functional in the CD2 transgenic mice and indicate a considerable conservation of the signal transducing processes and also the activation mechanisms between mouse and man.


Epidermal growth factor receptor inhibition augments the expression of MHC class I and II genes.
Diverse immune-related effects occur with the use of epidermal growth factor receptor inhibitors (EGFRI). In addition to the cutaneous inflammation induced by EGFRIs, these agents have been associated with the exacerbation of autoimmune skin disease and contact hypersensitivity, antiviral effects, and fatal alveolar damage in the setting of lung transplantation. Because EGFR ligands can modulate MHC class I (MHCI) and II (MHCII) molecule expression, we hypothesized that some of the immune-related effects of EGFRIs are due to direct effects on the expression of MHCI and/or MHCII molecules. Primary human keratinocytes and a malignant keratinocyte cell line (A431) were treated with EGFRIs alone or prior to IFN-γ, a potent inducer of MHCI and MHCII molecule expression. CIITA, MHCI, and MHCII RNA expression was measured using quantitative real-time reverse transcriptase PCR, and cell surface MHCI and MHCII protein expression was measured using flow cytometry. Skin biopsies from patients were analyzed for MHCI and MHCII protein expression before and during therapy with an EGFRI using immunohistochemistry. Both EGFR tyrosine kinase inhibitors and ligand-blocking antibodies (cetuximab) augmented the induction of MHCI and MHCII molecules by IFN-γ in primary and malignant human keratinocytes. Unexpectedly, the increase in MHCI protein expression did not require the presence of IFN-γ. Consistent with these in vitro findings, skin biopsies from cancer patients exhibited increased epidermal MHCI protein expression during therapy with an EGFRI as well as increases in MHCI and MHCII molecule RNA. These studies suggest that EGFRIs may influence immune/inflammatory responses by directly modulating MHC expression. Clin Cancer Res; 17(13); 4400-13. ©2011 AACR.


Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles.
In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients.


Association between transient interface fluid on intraoperative OCT and textural interface opacity after DSAEK surgery in the PIONEER study.
The aim of this study was to examine the association between transient interface fluid (TIF) and textural interface opacity (TIO) after Descemet stripping automated endothelial keratoplasty (DSAEK) surgery using intraoperative optical coherence tomography (iOCT) in the PIONEER (Prospective Intraoperative and Perioperative Ophthalmic ImagiNg with Optical CoherEncE TomogRaphy) study. All consecutive eyes that underwent DSAEK between October 2011 and September 2013 from the PIONEER intraoperative and perioperative OCT study were included. iOCT images were captured after lenticule apposition with complete air fill and after air-fluid exchange. Postoperative day 1 OCT images were obtained. Outcome variables included the presence of TIO at the graft-host junction and the presence of intraoperative and postoperative interface fluid on OCT. Seventy-six eyes from 69 patients who underwent DSAEK with iOCT were included. The mean age of the patients was 71 years (range 31-90). The 2 most common indications for surgery were Fuchs dystrophy (63%) and pseudophakic bullous keratopathy (24%). In 18 of 76 (23.7%) eyes, TIF was visible on iOCT post air-fluid exchange. Of these eyes, 14 developed TIO. TIO was observed in 18 of 76 (23.7%) eyes. TIF on iOCT was associated with a significantly higher rate of postoperative TIO (odds ratio = 47.25; P < 0.0001). Sixteen of the 18 eyes that had TIF on iOCT had had resolution on the postoperative day 1 OCT. There was no significant difference in the mean graft thickness between eyes with TIF on iOCT and those without (P = 0.58). Eyes with TIF on iOCT are more likely to develop TIO in the postoperative period. It is believed that the process of gap closure results in TIO, possibly secondary to precipitated solutes, retained viscoelastic, or lamellar irregularities caused by delayed adhesion or uneven matching of lamellar fibrils.


Complex biotic interactions drive long-term vegetation dynamics in a subarctic ecosystem.
Predicting impacts of global warming requires understanding of the extent to which plant biomass and production are controlled by bottom-up and top-down drivers. By annually monitoring community composition in grazed control plots and herbivore-free exclosures at an Arctic location for 15 years, we detected multiple biotic interactions. Regular rodent cycles acted as pulses driving synchronous fluctuations in the biomass of field-layer vegetation; reindeer influenced the biomass of taller shrubs, and the abundance of plant pathogenic fungi increased when densities of their host plants increased in exclosures. Two outbreaks of geometrid moths occurred during the study period, with contrasting effects on the field layer: one in 2004 had marginal effects, while one in 2012 severely reduced biomass in the control plots and eliminated biomass that had accumulated over 15 years in the exclosures. The latter was followed by a dramatic decline of the dominant understory dwarf-shrub Empetrum hermaphroditum, driven by an interaction between moth herbivory on top buds and leaves, and increased disease severity of a pathogenic fungus. We show that the climate has important direct and indirect effects on all these biotic interactions. We conclude that long time series are essential to identify key biotic interactions in ecosystems, since their importance will be influenced by climatic conditions, and that manipulative treatments are needed in order to obtain the mechanistic understanding needed for robust predictions of future ecosystem changes and their feedback effects.


Ordered coalescence of nanocrystals: a path to strong macroporous nanoceramics.
A versatile approach for integrating two apparently conflicting physical properties, high porosity and high mechanical strength, in polycrystalline bulks is established and demonstrated for the case of alumina ceramics. Macroporous alumina nanoceramics are synthesized by stimulating coalescence-mediated necking, which enables the formation of strong crystallographically coherent necks between adjacent grains. The work places a general emphasis on manipulating crystal growth on the nanoscale and on preparing highly porous polycrystalline bulk ceramics with improved mechanical rigidity.


The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation.
Extracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation. Mongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was performed before and at 1, 2, and 3 hours after ECC commencement. To eliminate bias induced by hematocrit and plasma, all blood samples were adjusted to a hematocrit of 45% using baseline plasma. Blood viscoelasticity, plasma viscosity, hematocrit, arterial blood gas analysis, central venous O2 saturation, and lactate were measured. The blood viscosity and aggregation index decreased abruptly 1 hour after ECC and then remained low during ECC in both groups, but blood elasticity did not change during ECC. Blood viscosity, blood elasticity, plasma viscosity, and the aggregation index were not significantly different in the groups at any time. Hematocrit decreased abruptly 1 hour after ECC in both groups due to dilution by the priming solution used. After ECC, blood viscoelasticity and RBC aggregation were not different in the pulsatile and nonpulsatile groups in the adult dog model. Furthermore, pulsatile flow did not have a more harmful effect on blood viscoelasticity or RBC aggregation than nonpulsatile flow.


Risk prediction models for mortality in ambulatory patients with heart failure: a systematic review.
Optimal management of heart failure requires accurate assessment of prognosis. Many prognostic models are available. Our objective was to identify studies that evaluate the use of risk prediction models for mortality in ambulatory patients with heart failure and describe their performance and clinical applicability. We searched for studies in Medline, Embase, and CINAHL in May 2012. Two reviewers selected citations including patients with heart failure and reporting on model performance in derivation or validation cohorts. We abstracted data related to population, outcomes, study quality, model discrimination, and calibration. Of the 9952 studies reviewed, we included 34 studies testing 20 models. Only 5 models were validated in independent cohorts: the Heart Failure Survival Score, the Seattle Heart Failure Model, the PACE (incorporating peripheral vascular disease, age, creatinine, and ejection fraction) risk score, a model by Frankenstein et al, and the SHOCKED predictors. The Heart Failure Survival Score was validated in 8 cohorts (2240 patients), showing poor-to-modest discrimination (c-statistic, 0.56-0.79), being lower in more recent cohorts. The Seattle Heart Failure Model was validated in 14 cohorts (16 057 patients), describing poor-to-acceptable discrimination (0.63-0.81), remaining relatively stable over time. Both models reported adequate calibration, although overestimating survival in specific populations. The other 3 models were validated in a cohort each, reporting poor-to-modest discrimination (0.66-0.74). Among the remaining 15 models, 6 were validated by bootstrapping (c-statistic, 0.74-0.85); the rest were not validated. Externally validated heart failure models showed inconsistent performance. The Heart Failure Survival Score and Seattle Heart Failure Model demonstrated modest discrimination and questionable calibration. A new model derived from contemporary patient cohorts may be required for improved prognostic performance.


Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32.
Genome-wide array-based comparative genomic hybridization analysis of malignant pleural mesotheliomas (MPM) was carried out to identify regions that display DNA copy number alterations. Seventeen primary tumors and nine cell lines derived from 22 individuals were studied, some of them originating from the same patients. Regions of genomic aberrations observed in >20% of individuals were 1q, 5p, 7p, 8q24 and 20p with gains, and 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 4q34-qter, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q with losses. Two regions at 1p32.1 and 11q22 showed a high copy gain. The 1p32.1 region contained a protooncogene, JUN, and we further demonstrated overexpression of JUN with real-time polymerase chain reaction analysis. As MPM cell lines did not overexpress JUN, our findings suggested that induction of JUN expression was involved in the development of MPM cells in vivo, which also might result in gene amplification in a subset of MPM. Meanwhile, the most frequent alteration was the 9p21.3 deletion, which includes the p16(INK4a)/p14(ARF) locus. With polymerase chain reaction analysis, we determined the extent of the homozygous deletion regions of the p16(INK4a)/p14(ARF) locus in MPM cell lines, which indicated that the deletion regions varied among cell lines. Our results with array comparative genomic hybridization analysis provide new insights into the genetic background of MPM, and also give some clues to develop a new molecular target therapy for MPM.


Interaction matrix uncertainty in active (and adaptive) optics.
Uncertainty in the interaction matrix between sensors and actuators can lead to performance degradation or instability in control of segmented mirrors (typically the telescope primary). The interaction matrix is ill conditioned, and thus the position estimate required for control can be highly sensitive to small errors in knowledge of the matrix, due to uncertainty or temporal variations. The robustness to different types of uncertainty is bounded here using the small gain theorem and structured singular values. The control is quite robust to moderate uncertainty in actuator gain, sensor gain, or the ratio of sensor dihedral and height sensitivity. However, the control is extremely sensitive to small errors in geometry, with the maximum error that can be tolerated scaling inversely with the number of segments. The same tools can be applied to adaptive optics; however, the interaction matrix here is better conditioned and so uncertainty is less of an issue, with the tolerable error scaling inversely with the square root of the number of actuators.


Evaluation of efficacy of photodynamic therapy as an adjunct to nonsurgical periodontal therapy in treatment of chronic periodontitis patients: A clinico-microbiological study.
Photodynamic therapy (PDT) is a local noninvasive treatment modality without side effects caused by antibiotics. The aim of this study was to evaluate the efficacy of adjunctive use of PDT with scaling and root planing as compared with SRP alone in the treatment of chronic periodontitis. Twenty participants with chronic periodontitis having probing pocket depths (PDs) of ≥5 mm were selected for the study. Patients were randomly divided into control group and test group with ten patients in each group. Full-mouth SRP was performed in both the groups, followed by PDT in test group. Assessment of plaque index (PI), gingival index (GI), PD, and clinical attachment level (CAL) was done at baseline and after 3 months. Microbiological assessment of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola was done by polymerase chain reaction (PCR) at baseline and 3 months after the therapy. There was a significant reduction in PI, GI, PD, CAL, and microbiologic parameters in test group, following SRP and PDT, when compared with SRP alone in control group. PDT in conjunction with SRP has shown additional improvement in periodontal parameters when compared to SRP alone and has a beneficial effect in chronic periodontitis patients.


Patients, health professionals, and the health system: influencers on patients' participation in ward rounds.
The ward round is an opportunity to plan and deliver patient-centered care. Benefits include an effective and safer clinician-patient relationship, patient empowerment, reduced anxiety and increased trust in the health care system. Factors contributing to patient involvement in ward rounds is shaped by their preferences, ability, and opportunity. To investigate ward rounds and the patient experience with them, the relationship between the patient and clinicians, and how rounds facilitate collaboration between them. A multimethod study was conducted in a single Australian facility in acute medicine and rehabilitation specialties. An observational study of ward rounds in each setting was conducted with 14 patients, aged between 55 and 89 years followed by semi-structured interviews conducted with the patients observed. Descriptive and thematic analysis was undertaken. One third of participants had not heard of the term ward round or could describe their purpose. Three main influencers on the patient experience of rounds were: self; the health system; and medical officers. No meaningful difference was found between patients in acute medicine and rehabilitation although all wanted to receive information from the senior medical officers. Patients more familiar with the health system were more active participants and took greater responsibility for their involvement in rounds and described higher satisfaction. There is a level of acceptance within the health system that patients understand what a ward round is. However, their role on the round is complex and this may only be developed through experiencing them. High system users teach themselves to navigate rounding processes to ensure their needs are met. To ensure equity in participation patients should be educated on ward rounds, what to expect and how to they can participate.


Calvarial hyperostosis syndrome in two bullmastiffs.
Two bullmastiffs with calvarial hyperostosis syndrome are described and are the first documented examples in females. The clinical and radiologic features were similar to those previously reported in males. Magnetic resonance (MR) imaging findings have not previously been reported. One dog underwent MR imaging and abnormalities included thickening of the frontal bones with loss of normal fat signal and changes in the overlying soft tissues. In one of the dogs, long bone changes were seen in the femora and resembled those seen with craniomandibular osteopathy.


Synergistic inhibition of HIV-1 infection by combinations of soluble polyanions with other potential microbicides.
Several polyanionic compounds with potential for use as topically applied microbicides to prevent HIV-1 sexual transmission, such as PRO 2000, are currently in phase III clinical efficacy trials. Microbicidal formulations may well comprise combinations of inhibitors to increase potency, reduce dose and minimize problems of HIV-1 resistance. We have therefore evaluated in vitro, the anti-HIV-1 activity of two leading polyanionic microbicides combined with other antiretroviral agents with microbicidal potential. Dextran sulfate (DS) and PRO 2000 were combined with the neutralizing antibody IgG1b12, the peptide-based fusion inhibitor T20, the CCR5 antagonist TAK779 and the cyanobacterial protein cyanovirin-N. Anti-HIV-1 activity was assessed in a single cycle replication assay using pseudoviruses carrying a luciferase reporter gene and the envelope glycoproteins from HIV-1 isolates JR-FL (R5) and HxB2 (X4), against both immortalized and primary CD4+ cell targets. The data were analyzed for synergy using Calcusyn software. Results indicate that PRO 2000 and DS can act synergistically with most inhibitors tested, although the degree of synergy depends on inhibitor concentration and combination. These data provide a rational basis for testing of microbicide combinations in vivo.


Acclimating Cucumber Plants to Blue Supplemental Light Promotes Growth in Full Sunlight.
Raising young plants is important for modern greenhouse production. Upon transfer from the raising to the production environment, young plants should maximize light use efficiency while minimizing deleterious effects associated with exposure to high light (HL) intensity. The light spectrum may be used to establish desired traits, but how plants acclimated to a given spectrum respond to HL intensity exposure is less well explored. Cucumber (Cucumis sativus) seedlings were grown in a greenhouse in low-intensity sunlight (control; ∼2.7 mol photons m-2 day-1) and were treated with white, red, blue, or green supplemental light (4.3 mol photons m-2 day-1) for 10 days. Photosynthetic capacity was highest in leaves treated with blue light, followed by white, red, and green, and was positively correlated with leaf thickness, nitrogen, and chlorophyll concentration. Acclimation to different spectra did not affect the rate of photosynthetic induction, but leaves grown under blue light showed faster induction and relaxation of non-photochemical quenching (NPQ) under alternating HL and LL intensity. Blue-light-acclimated leaves showed reduced photoinhibition after HL intensity exposure, as indicated by a high maximum quantum yield of photosystem II photochemistry (F v /F m ). Although plants grown under different supplemental light spectra for 10 days had similar shoot biomass, blue-light-grown plants (B-grown plants) showed a more compact morphology with smaller leaf areas and shorter stems. However, after subsequent, week-long exposure to full sunlight (10.7 mol photons m-2 day-1), B-grown plants showed similar leaf area and 15% higher shoot biomass, compared to plants that had been acclimated to other spectra. The faster growth rate in blue-light-acclimated plants compared to other plants was mainly due to a higher photosynthetic capacity and highly regulated NPQ performance under intermittent high solar light. Acclimation to blue supplemental light can improve light use efficiency and diminish photoinhibition under high solar light exposure, which can benefit plant growth.


Sex determination in mammals--before and after the evolution of SRY.
Therian mammals (marsupials and placentals) have an XX female: XY male sex chromosome system, which is homologous to autosomes in other vertebrates. The testis-determining gene, SRY, is conserved on the Y throughout therians, but is absent in other vertebrates, suggesting that the mammal system evolved about 310 million years ago (MYA). However, recent work on the basal monotreme mammals has completely changed our conception of how and when this change occurred. Platypus and echidna lack SRY, and the therian X and Y are represented by autosomes, implying that SRY evolved in therians after their divergence from monotremes only 166 MYA. Clues to the ancestral mechanism usurped by SRY in therians are provided by the monotremes, whose sex chromosomes are homologous to the ZW of birds. This suggests that the therian X and Y, and the SRY gene, evolved from an ancient bird-like sex chromosome system which predates the divergence of mammals and reptiles 310 MYA.


The major outer membrane protein OmpU of Vibrio splendidus contributes to host antimicrobial peptide resistance and is required for virulence in the oyster Crassostrea gigas.
Vibrio splendidus, strain LGP32, is an oyster pathogen associated with the summer mortalities affecting the production of Crassostrea gigas oysters worldwide. Vibrio splendidus LGP32 was shown to resist to up to 10 microM Cg-Def defensin and Cg-BPI bactericidal permeability increasing protein, two antimicrobial peptides/proteins (AMPs) involved in C. gigas immunity. The resistance to both oyster Cg-Def and Cg-BPI and standard AMPs (polymyxin B, protegrin, human BPI) was dependent on the ompU gene. Indeed, upon ompU inactivation, minimal bactericidal concentrations decreased by up to fourfold. AMP resistance was restored upon ectopic expression of ompU. The susceptibility of bacterial membranes to AMP-induced damages was independent of the ompU-mediated AMP resistance. Besides its role in AMP resistance, ompU proved to be essential for the adherence of V. splendidus LGP32 to fibronectin. Interestingly, in vivo, ompU was identified as a major determinant of V. splendidus pathogenicity in oyster experimental infections. Indeed, the V. splendidus-induced oyster mortalities dropped from 56% to 11% upon ompU mutation (Kaplan-Meier survival curves, P < 0.01). Moreover, in co-infection assays, the ompU mutant was out competed by the wild-type strain with competitive indexes in the range of 0.1-0.2. From this study, ompU is required for virulence of V. splendidus. Contributing to AMP resistance, conferring adhesive properties to V. splendidus, and being essential for in vivo fitness, the OmpU porin appears as an essential effector of the C. gigas/V. splendidus interaction.


Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins.
Atherogenesis is an inflammatory process with leukocytes infiltrating the arterial intima. The lipoxygenase pathways play a role in leukocyte recruitment through the generation of two classes of arachidonic acid lipid mediators, the leukotrienes and the lipoxins, and one class of omega-3 fatty acid metabolites, the resolvins. There is evidence from animal studies and human genetic studies that the leukotrienes and the enzymes necessary for their generation play a role in atherosclerosis, and possibly even in the development of the vulnerable plaque. Less is known about the effect of the anti-inflammatory lipid mediators in atherosclerosis, the lipoxins and the resolvins. Studies modulating the activity of an enzyme necessary for the production of these lipid mediators, 12/15-lipoxygenase, showed discrepant results in several animal models. Also, human genetic studies have not clearly dissected the effect of the enzyme on atherosclerosis. However, stable forms of the lipoxins and the resolvins protect animals from inflammatory diseases. Whether blocking the leukotrienes or applying anti-inflammatory lipoxins and resolvins will be effective in attenuating human atherosclerosis needs to be demonstrated in future studies. In this review, the biosynthesis of these lipid mediators, their biological effects and the evidence for their possible role in atherosclerosis are discussed with an emphasis on human disease.


Current concept in rotational laxity control and evaluation in ACL reconstruction.
Rotation combined with translation; compose the three-dimensional motion of the knee subluxation in anterior cruciate ligament deficient knee. The worldwide scientists were focused initially on the translation part of this complex 3D motion, but since the beginning of the century there was a large interest on knee rotational laxity study. Lot of paper reported new devices and results with an explosion since the beginning of the decade. The purpose of this review is to provide an extensive critical analysis of the literature and clarify the knowledge on this topic. We will start with a dismemberment of different rotational laxities reported: the rotation coupled with translation in 2D tests such as Lachman test and anterior drawer test; the rotational envelope considering the maximum internal external rotation; and the "active rotation" occurring in 3D Pivot-shift (PS) test. Then we will analyze the knee kinematics and the role of different anterior cruciate ligament (ACL) bundle on rotation. A review of different mechanical and radiological devices used to assess the different rotations on ACL deficient knees will be presented. Two groups will be analyzed, dynamic and static conditions of tests. Navigation will be described precisely; it was the starter of this recent interest in rotation studies. Opto electronic and electromagnetic navigation systems will be presented and analyzed. We will conclude with the last generation of rotational laxity assessment devices, using accelerometers, which are very promising.


IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells.
Natural Abs, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis, but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neoantigenic determinants on apoptotic thymocytes is dominated by Abs to oxidation-associated Ags, phosphorylcholine (PC), a head group that becomes exposed during programmed cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive oxidation species. While natural Abs to apoptotic cells in naive adult mice were dominated by PC and MDA specificities, the amounts of these Abs were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA Abs was affected by V(H) gene inheritance. Ab interactions with apoptotic cells also mediated the recruitment of C1q, which enhanced apoptotic cell phagocytosis by immature dendritic cells. Significantly, IgM Abs to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural Abs that recognize neoantigens on apoptotic cells, in naive mice and those induced by immune exposure to apoptotic cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells.


South Africa's cataract surgery rates: why are we not meeting our targets?
Cataract is the leading cause of blindness in South Africa, responsible for about 50% of the prevalence of blindness and identified as a national health priority. The cataract surgery rate (CSR) should be at least 2 000 per million population per year for elimination of cataract blindness. The national CSR target was planned to increase from 1 000 in 2005 to 2 000 in 2010, but since CSRs have failed to reach targets each year, the national target for 2010 was reduced from 2 000 to 1 500. We reviewed data from a situational analysis in 2007 of cataract surgery services to ascertain the obstacles to achieving CSR targets.


Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome.
Aspergillus fumigatus, an opportunistic human pathogen, frequently infects the lungs of people with cystic fibrosis and is one of the most common causes of infectious-disease death in immunocompromised patients. Here, we construct 252 strain-specific, genome-scale metabolic models of this important fungal pathogen to study and better understand the metabolic component of its pathogenic versatility. The models show that 23.1% of A. fumigatus metabolic reactions are not conserved across strains and are mainly associated with amino acid, nucleotide, and nitrogen metabolism. Profiles of non-conserved reactions and growth-supporting reaction fluxes are sufficient to differentiate strains, for example by environmental or clinical origin. In addition, shotgun metagenomics analysis of sputum from 40 cystic fibrosis patients (15 females, 25 males) before and after diagnosis with an A. fumigatus colonization suggests that the fungus shapes the lung microbiome towards a more beneficial fungal growth environment associated with aromatic amino acid availability and the shikimate pathway. Our findings are starting points for the development of drugs or microbiome intervention strategies targeting fungal metabolic needs for survival and colonization in the non-native environment of the human lung.


First Report of Powdery Mildew Caused by Erysiphe heraclei on Dill in Korea.
Dill (Anethum graveolens L.) is a scented herb belonging to the family Apiaceae. The plant has a long and ancient history in many countries as a culinary and medicinal herb. In October 2008, plants showing typical symptoms of powdery mildew disease were found in polythene tunnels in Icheon, Korea. Symptoms first appeared as thin white colonies, which subsequently showed abundant growth on the leaves and stems. Most diseased plantings were unmarketable and shriveled without being harvested. The damage caused by powdery mildew infections on dill has reappeared every year, with confirmation of the causal agent made again in 2011. Voucher specimens were deposited in the Korea University Herbarium (KUS). Hyphae were septate, branched, and 4 to 7 μm wide. Appressoria on the mycelium were multilobed or moderately lobed. Conidiophores were unbranched, cylindrical, 80 to 140 × 8 to 10 μm, straight or slightly flexuous in foot cells, and produced conidia singly, followed by two to three cells. Conidia were oblong elliptical to oblong, 28 to 50 × 14 to 18 μm, lacked fibrosin bodies, and produced germ tubes on the subterminal position, with angular/rectangular wrinkling of the outer walls. Primary conidia were apically conical, basally subtruncate, and generally smaller than the secondary conidia. No chasmothecia were found but the above characteristics are consistent with Erysiphe heraclei DC. (1). To confirm the identity of the causal fungus, the complete internal transcribed spacer (ITS) region of rDNA from isolate KUS-F26425 was amplified with primers ITS5 and P3 as described by Takamatsu et al. (3) and directly sequenced. The resulting 630-bp sequence was deposited in GenBank (Accession No. JQ517297). Comparison with the sequences available in the GenBank database revealed that the isolate showed >99% sequence similarity with those of E. heraclei from Pleurospermum camtschaticum (GU173850) and Daucus carota (EU371725). Pathogenicity was confirmed through inoculation by gently pressing diseased leaves onto leaves of five healthy potted dill plants. Five noninoculated plants served as controls. Plants were maintained in a greenhouse at 22 ± 2°C. Inoculated plants developed signs and symptoms after 7 days, whereas the control plants remained healthy. The fungus present on the inoculated plants was morphologically identical to that originally observed on diseased plants. Powdery mildew caused by E. heraclei on dill has been known worldwide where the plant is cultivated (2). In East Asia, however, dill powdery mildew was known only from Taiwan (4). To our knowledge, this is the first report of powdery mildew infections by E. heraclei on dill in Korea. Since cultivation of dill was only recently started on a commercial scale in Korea, powdery mildew infections pose a serious threat to safe production of this herb, especially in organic farming where chemical control would be prohibited. References: (1) U. Braun. Beih. Nova Hedw. 89:1, 1987. (2) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ January 28, 2012. (3) S. Takamatsu et al. Mycol. Res. 113:117, 2009. (4) J. G. Tsay. Trans. Mycol. Soc. Repub. China 5:1, 1990.


Identifying paediatric nursing-sensitive outcomes in linked administrative health data.
There is increasing interest in the contribution of the quality of nursing care to patient outcomes. Due to different casemix and risk profiles, algorithms for administrative health data that identify nursing-sensitive outcomes in adult hospitalised patients may not be applicable to paediatric patients. The study purpose was to test adult algorithms in a paediatric hospital population and make amendments to increase the accuracy of identification of hospital acquired events. The study also aimed to determine whether the use of linked hospital records improved the likelihood of correctly identifying patient outcomes as nursing sensitive rather than being related to their pre-morbid conditions. Using algorithms developed by Needleman et al. (2001), proportions and rates of records that identified nursing-sensitive outcomes for pressure ulcers, pneumonia and surgical wound infections were determined from administrative hospitalisation data for all paediatric patients discharged from a tertiary paediatric hospital in Western Australia between July 1999 and June 2009. The effects of changes to inclusion and exclusion criteria for each algorithm on the calculated proportion or rate in the paediatric population were explored. Linked records were used to identify comorbid conditions that increased nursing-sensitive outcome risk. Rates were calculated using algorithms revised for paediatric patients. Linked records of 129,719 hospital separations for 79,016 children were analysed. Identification of comorbid conditions was enhanced through access to prior and/or subsequent hospitalisation records (43% of children with pressure ulcers had a form of paralysis recorded only on a previous admission). Readmissions with a surgical wound infection were identified for 103 (4.8/1,000) surgical separations using linked data. After amendment of each algorithm for paediatric patients, rates of pressure ulcers and pneumonia reduced by 53% and 15% (from 1.3 to 0.6 and from 9.1 to 7.7 per 10,000 patient days) respectively, and an 84% increase in the proportion of surgical wound infection (from 5.7 to 10.4 per 1,000 separations). Algorithms for nursing-sensitive outcomes used in adult populations have to be amended before application to paediatric populations. Using unlinked individual hospitalisation records to estimate rates of nursing-sensitive outcomes is likely to result in inaccurate rates.


Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles.
We outline a strategy to enable non-directed Pd(II)-catalyzed C-H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C-H acetoxylation reactions, addition of a variety of N-containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effective in situ blocking groups for the Lewis basic site, and a pre-formed pyridine N-oxide is shown to enable high yield of allylic C-H acetoxylation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2 provide an inverse correlation of the computed heterocycle-Pd(OAc)2 binding affinities with the experimental conversions to products. Additionally, 1H NMR binding studies provide experimental support for theoretical calculations.


Improving Standards of Care in Obstructed Labour: A Criteria-Based Audit at a Referral Hospital in a Low-Resource Setting in Tanzania.
In low-resource settings, obstructed labour is strongly associated with severe maternal morbidity and intrapartum asphyxia, and consequently maternal and perinatal deaths. This study evaluated the impact of a criteria-based audit of the diagnosis and management of obstructed labour in a low-resource setting. A baseline criteria-based audit was conducted from October 2013 to March 2014, followed by a workshop in which stakeholders gave feedback on interventions agreed upon to improve obstetric care. The implemented interventions included but were not limited to introducing standard guidelines for diagnosis and management of obstructed labour, agreeing on mandatory review by specialist for cases that are assigned caesarean section, re-training and supervision on use and interpretation of partograph and, strengthening team work between doctors, mid-wives and theatre staff. After implementing these interventions in March, a re-audit was performed from July 2015 to November, 2015, and the results were compared to those of the baseline audit. Two hundred and sixty deliveries in the baseline survey and 250 deliveries in the follow-up survey were audited. Implementing the new criteria improved the diagnosis from 74% to 81% (p = 0.049) and also the management of obstructed labour from 4.2% at baseline audit to 9.2% at re-audit (p = 0.025). Improved detection of prolonged labour through heightened observation of regular contractions, protracted cervical dilatation, protracted descent of presenting part, arrested cervical dilation, and severe moulding contributed to improved standards of diagnosis (all p < 0.04). Patient reviews by senior obstetricians increased from 34% to 43% (p = 0.045) and reduced time for caesarean section intervention from the median time of 120 to 90 minutes (p = 0.001) improved management (all p < 0.05). Perinatal outcomes, neonatal distress and fresh stillbirths, were reduced from 16% to. 8.8% (p = 0.01). A criteria-based audit proved to be a feasible and useful tool in improving diagnosis and management of obstructed labour using available resources. Some of the observed changes in practice were of modest magnitude implying demand for further improvements, while sustaining those already put in place.


The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins.
Although transcription and pre-mRNA processing are colocalized in eukaryotic nuclei, molecules linking these processes have not previously been described. We have identified four novel rat proteins by their ability to interact with the repetitive C-terminal domain (CTD) of RNA polymerase II in a yeast two-hybrid assay. A yeast homolog of one of the rat proteins has also been shown to interact with the CTD. These CTD-binding proteins are all similar to the SR (serine/arginine-rich) family of proteins that have been shown to be involved in constitutive and regulated splicing. In addition to alternating Ser-Arg domains, these proteins each contain discrete N-terminal or C-terminal CTD-binding domains. We have identified SR-related proteins in a complex that can be immunoprecipitated from nuclear extracts with antibodies directed against RNA polymerase II. In addition, in vitro splicing is inhibited either by an antibody directed against the CTD or by wild-type but not mutant CTD peptides. Thus, these results suggest that the CTD and a set of CTD-binding proteins may act to physically and functionally link transcription and pre-mRNA processing.


On the prediction of the el nino of 1986-1987.
Three different classes of numerical models successfully predicted the occurrence of the El Niño of 1986-87 at lead times of 3 to 9 months. Although the magnitude and timing of predicted ocean surface temperatures were not perfect, these results suggest that routine prediction of moderate to lare El Niño events is feasible. The key to the success of the models lies in recognizing or simulating the low-frequency, large-scale changes in the tropical ocean-atmosphere system that give rise to El Niño events.


The search for migraine genes: an overview of current knowledge.
Migraine is a complex familial condition that imparts a significant burden on society. There is evidence for a role of genetic factors in migraine, and elucidating the genetic basis of this disabling condition remains the focus of much research. In this review we discuss results of genetic studies to date, from the discovery of the role of neural ion channel gene mutations in familial hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the more common forms of migraine. The success of FHM regarding discovery of genetic defects associated with the disorder remains elusive in common migraine, and causative genes have not yet been identified. Thus we suggest additional approaches for analysing the genetic basis of this disorder. The continuing search for migraine genes may aid in a greater understanding of the mechanisms that underlie the disorder and potentially lead to significant diagnostic and therapeutic applications.


Human origins in a southern African palaeo-wetland and first migrations.
Anatomically modern humans originated in Africa around 200 thousand years ago (ka)1-4. Although some of the oldest skeletal remains suggest an eastern African origin2, southern Africa is home to contemporary populations that represent the earliest branch of human genetic phylogeny5,6. Here we generate, to our knowledge, the largest resource for the poorly represented and deepest-rooting maternal L0 mitochondrial DNA branch (198 new mitogenomes for a total of 1,217 mitogenomes) from contemporary southern Africans and show the geographical isolation of L0d1'2, L0k and L0g KhoeSan descendants south of the Zambezi river in Africa. By establishing mitogenomic timelines, frequencies and dispersals, we show that the L0 lineage emerged within the residual Makgadikgadi-Okavango palaeo-wetland of southern Africa7, approximately 200 ka (95% confidence interval, 240-165 ka). Genetic divergence points to a sustained 70,000-year-long existence of the L0 lineage before an out-of-homeland northeast-southwest dispersal between 130 and 110 ka. Palaeo-climate proxy and model data suggest that increased humidity opened green corridors, first to the northeast then to the southwest. Subsequent drying of the homeland corresponds to a sustained effective population size (L0k), whereas wet-dry cycles and probable adaptation to marine foraging allowed the southwestern migrants to achieve population growth (L0d1'2), as supported by extensive south-coastal archaeological evidence8-10. Taken together, we propose a southern African origin of anatomically modern humans with sustained homeland occupation before the first migrations of people that appear to have been driven by regional climate changes.


Advancements in the development of HIF-1α-activated protein switches for use in enzyme prodrug therapy.
While gene-directed enzyme prodrug therapy has shown potential as a cancer therapeutic in animal and clinical trials, concerns over the efficacy, selectivity, and safety of gene delivery vehicles have restricted its advance. In an attempt to relieve some of the demands on targeted gene delivery vehicles and achieve the full potential of enzyme prodrug therapy, cancer-targeted activity can be engineered into the enzyme itself. We previously engineered a switchable prodrug-activating enzyme that selectively kills human cancer cells accumulating the cancer marker hypoxia-inducible factor-1α (HIF-1α). This HIF-1α-activated protein switch (Haps59) is designed to increase its ability to convert the prodrug 5-fluorocytosine into the chemotherapeutic 5-fluorouracil in a HIF-1α-dependent manner. However, in cancer cell lines expressing Haps59 the 5FC sensitivity difference between the presence and absence of HIF-1α was not as large as desired. In this work, we aimed to improve the cancer specificity of this switch via a directed evolution approach utilizing random mutagenesis, linker mutagenesis, and random insertion and circular permutation. We identified improved HIF-1α-activated protein switches that confer E. coli with modest increases in HIF-1α-dependent 5FC toxicity. Additionally, the current bottleneck in the development of improved HIF-1α-activated protein switches is screening switch candidates in mammalian cells. To accommodate higher throughput and reduce experimental variability, we explored the use of Flp recombinase-mediated isogenic integration in 293 cells. These experiments raised the possibility that Haps59 can be activated by other interactors of the CH1 domain, and experiments in E. coli indicated that CITED2 can also activate Haps59. Although many CH1 binding partners are also oncogenes, CH1's promiscuous binding and subsequent off-target activation of Haps59 needs to be examined under normal physiological conditions to identify off-target activators. With aberrant activating molecules identified, further directed evolution can be performed to improve the cancer specificity of HIF-1α-activated protein switches.


Cardiac rehabilitation after acute myocardial infarction in Sweden - evaluation of programme characteristics and adherence to European guidelines: The Perfect Cardiac Rehabilitation (Perfect-CR) study.
While patient performance after participating in cardiac rehabilitation programmes after acute myocardial infarction is regularly reported through registry and survey data, information on cardiac rehabilitation programme characteristics is less well described. The aim of this study was to evaluate Swedish cardiac rehabilitation programme characteristics and adherence to European Guidelines on Cardiovascular Disease Prevention. Cardiac rehabilitation programme characteristics at all 78 cardiac rehabilitation centres in Sweden in 2016 were surveyed using a web-based questionnaire (100% response rate). The questions were based on core components of cardiac rehabilitation as recommended by European Guidelines. There was a wide variation in programme duration (2-14 months). All programmes reported offering an individual post-discharge visit with a nurse, and 90% (n = 70) did so within three weeks from discharge. Most programmes offered centre-based exercise training (n = 76, 97%) and group educational sessions (n = 61, 78%). All programmes reported to the national audit, SWEDEHEART, and 60% (n = 47) reported that performance was regularly assessed using audit data, to improve quality of care. Ninety-six per cent (n = 75) had a core team consisting of a cardiologist, a physiotherapist and a nurse and 76% (n = 59) reported having a medical director. Having other allied healthcare professionals included in the cardiac rehabilitation team varied. Forty per cent (n = 31) reported having regular team meetings where nurses, physiotherapists and cardiologist could discuss patient cases. The overall quality of cardiac rehabilitation programmes provided in Sweden is high. Still, there are several areas of potential improvement. Monitoring programme characteristics as well as patient outcomes might improve programme quality and patient outcomes both at a local and a national level.


Superchirped moiré grating based on an acousto-optic superlattice with a chirped fiber Bragg grating.
A superchirped moiré grating has multiple superimposed chirped Bragg gratings. We show that a superchirped moiré grating can be formed in an acousto-optic superlattice with a chirped fiber Bragg grating. There are multiple transmission peaks related to Fabry-Perot resonance in the transmission spectrum. The peak spacing is varied by the acoustic frequency. The proposed devices can be used as tunable multiple-passband transmission filters and switches.


Cemented versus cementless Oxford unicompartmental knee arthroplasty using radiostereometric analysis: a randomised controlled trial.
The most common reasons for revision of unicompartmental knee arthroplasty (UKA) are loosening and pain. Cementless components may reduce the revision rate. The aim of this study was to compare the fixation and clinical outcome of cementless and cemented Oxford UKAs. A total of 43 patients were randomised to receive either a cemented or a cementless Oxford UKA and were followed for two years with radiostereometric analysis (RSA), radiographs aligned with the bone-implant interfaces and clinical scores. The femoral components migrated significantly during the first year (mean 0.2 mm) but not during the second. There was no significant difference in the extent of migration between cemented and cementless femoral components in either the first or the second year. In the first year the cementless tibial components subsided significantly more than the cemented components (mean 0.28 mm (sd 0.17) vs. 0.09 mm (sd 0.19 mm)). In the second year, although there was a small amount of subsidence (mean 0.05 mm) there was no significant difference (p = 0.92) between cemented and cementless tibial components. There were no femoral radiolucencies. Tibial radiolucencies were narrow (< 1 mm) and were significantly (p = 0.02) less common with cementless (6 of 21) than cemented (13 of 21) components at two years. There were no complete radiolucencies with cementless components, whereas five of 21 (24%) cemented components had complete radiolucencies. The clinical scores at two years were not significantly different (p = 0.20). As second-year migration is predictive of subsequent loosening, and as radiolucency is suggestive of reduced implant-bone contact, these data suggest that fixation of the cementless components is at least as good as, if not better than, that of cemented devices.


Soil metaproteomics - Comparative evaluation of protein extraction protocols.
Metaproteomics and its potential applications are very promising to study microbial activity in environmental samples and to obtain a deeper understanding of microbial interactions. However, due to the complexity of soil samples the exhaustive extraction of proteins is a major challenge. We compared soil protein extraction protocols in terms of their protein extraction efficiency for two different soil types. Four different protein extraction procedures were applied based on (a) SDS extraction without phenol, (b) NaOH and subsequent phenol extraction, (c) SDS-phenol extraction and (d) SDS-phenol extraction with prior washing steps. To assess the suitability of these methods for the functional analysis of the soil metaproteome, they were applied to a potting soil high in organic matter and a forest soil. Proteins were analyzed by two-dimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) and the number of unique spectra as well as the number of assigned proteins for each of the respective protocols was compared. In both soil types, extraction with SDS-phenol (c) resulted in "high" numbers of proteins. Moreover, a spiking experiment was conducted to evaluate protein recovery. To this end sterilized forest soil was amended with proteins from pure cultures of Pectobacterium carotovorum and Aspergillus nidulans. The protein recovery in the spiking experiment was almost 50%. Our study demonstrates that a critical evaluation of the extraction protocol is crucial for the quality of the metaproteomics data, especially in highly complex samples like natural soils.


Pulp revascularization of a necrotic infected immature permanent tooth: case report and review of the literature.
The purpose of this report was to present the case of a patient wherein revascularization of the necrotic infected pulp space of an immature permanent maxillary central incisor tooth was induced in vivo by stimulation of a blood clot from the periapical tissues into the canal space. This was achieved after disinfection of the canal space with a topical antibiotic paste followed by a blood clot scaffold induced from the periapical tissues. This treatment approach offers clinicians great potential to avoid the need for traditional apexification with calcium hydroxide or the need to achieve an artificial apical barrier with mineral trioxide aggregate. Furthermore, this treatment approach can help rescue infected immature teeth by physiologically strengthening the root walls.


Impact of individual anatomy on the benefit of cup medialisation in total hip arthroplasty.
In total hip arthroplasty, cup medialisation with compensatory increase of femoral offset has been proposed to increase the moment arms of abductor muscles. However, this technique is associated with a loss of acetabular bone stock. Previous data indicates that the potential benefit is not constant among patients and is likely related to patient anatomy. Therefore, to be able to select patients who would benefit most from this technique, we measured several anatomical parameters of the pelvis and femur in 15 patients; and evaluated correlations between them and the changes of moment arms associated with cup medialisation. The anatomical measurements were performed on 3-D reconstructions of preoperative CT scans. The moment arms of the gluteus medius and gluteus minimus were calculated for an abduction and flexion movement using patient-specific finite element models. 6 anatomical parameters were correlated with muscle moment arm variations after cup medialisation. This effect was not systematic for either muscles or movements. Among all parameters, femoral anteversion was the most important parameter in explaining the effect of cup medialisation. Patients with small femoral anteversion or low-riding greater trochanter benefit more from cup medialisation in terms of moment arm increase in abduction motion.


Exposure to metal oxide nanoparticles administered at occupationally relevant doses induces pulmonary effects in mice.
In spite of the great promises that the development of nanotechnologies can offer, concerns regarding potential adverse health effects of occupational exposure to nanoparticle (NP) is raised. We recently identified metal oxide NP in lung tissue sections of welders, located inside macrophages infiltrated in fibrous regions. This suggests a role of these NP in the lung alterations observed in welders. We therefore designed a study aimed to investigate the pulmonary effects, in mice, of repeated exposure to NP administered at occupationally relevant doses. We therefore chose four metal oxide NPs representative of those found in the welder's lungs: Fe2O3, Fe3O4, MnFe2O4 and CrOOH. These NPs were administered weekly for up to 3 months at two different doses: 5 μg, chosen as occupationally relevant to welding activity, and 50 μg, chosen as occupationally relevant to the context of an NP-manufacturing facility. Our results show that 3 month-repeated exposures to 5 μg NP induced limited pulmonary effects, characterized by the development of a mild peribronchiolar fibrosis observed for MnFe2O4 and CrOOH NP only. This fibrotic event was further extended in terms of intensity and localization after the repeated administration of 50 μg NP: all but Fe2O3 NP induced the development of peribronchiolar, perivascular and alveolar fibrosis, together with an interstitial inflammation. Our data demonstrate for the first time a potential risk for respiratory health posed by repeated exposure to NP at occupationally relevant doses. Given these results, the development of occupational exposure limits (OELs) specifically dedicated to NP exposure might therefore be an important issue to address.


Biological activity of some oxygenated sterols.
A group of oxygenated sterols has been identified as potent and specific inhibitors of sterol biosynthesis. The ability of these compounds to inhibit sterol synthesis in cultured cells and the ineffectiveness of cholesterol under the same conditions suggest that feedback regulation of sterol biosynthesis may be brought about by an oxygenated sterol rather than by cholesterol. The nature of the regulatory sterol may vary in different cells with their specific requirements for cholesterol as a structural component or as a precursor of other steroid products. The use of oxygenated sterols to block sterol synthesis in cultured cells provides new information regarding the role of sterol in cell membrane structure and function. For example, de novo sterol synthesis is required for DNA synthesis and cell division by some cultured cells. Studies with cultured cells, and with rats and mice in vivo, suggest that oxygenated sterols could be of value in the treatment of several important human diseases.


Elevated MiR-222-3p promotes proliferation and invasion of endometrial carcinoma via targeting ERα.
MicroRNAs play key roles in tumor proliferation and invasion. Here we show distinct expression of miR-222-3p between ERα-positive and ERα-negative endometrial carcinoma (EC) cell lines and primary tumors, and investigation of its relationship with ERα and other clinical parameters. In vitro, the function of miR-222-3p was examined in RL95-2 and AN3CA cell lines. MiR-222-3p expression was negatively correlated with ERα. Over-expressed miR-222-3p in RL95-2 cells promoted cell proliferation, enhanced invasiveness and induced a G1 to S phase shift in cell cycle. Furthermore, the miR-222-3p inhibitor decreased the activity of AN3CA cells to proliferate and invade. In vivo, down-regulated miR-222-3p of AN3CA cells inhibited EC tumor growth in a mouse xenograft model. Additionally, miR-222-3p increased raloxifene resistance through suppressing ERα expression in EC cells. In conclusion, miR-222-3p plays a significant role in the regulation of ERα expression and could be potential targets for restoring ERα expression and responding to antiestrogen therapy in a subset of ECs.


A randomized controlled trial of mindfulness-based stress reduction to manage affective symptoms and improve quality of life in gay men living with HIV.
To determine whether MBSR groups would help gay men living with HIV improve psychosocial functioning and increase mindfulness compared to treatment-as-usual (TAU). 117 participants were randomized 2:1 to MBSR or TAU. No new psychosocial or psychopharmacological interventions were initiated within 2 months of baseline. Standardized questionnaires were administered pre-, postintervention and at 6 months. An intent-to-treat analysis found significant benefits of MBSR: at post-intervention and 6 months follow up, MBSR participants had significantly lower avoidance in IES and higher positive affect compared to controls. MBSR participants developed more mindfulness as measured by the Toronto Mindfulness Scale (TMS) including both TMS subscales, curiosity and decentering, at 8-week and 6 months. For the sample as a whole, increase in mindfulness was significantly correlated with reduction in avoidance, higher positive affect and improvement in depression at 6 months. MBSR has specific and clinically meaningful effects in this population.


Lifestyle factors and health outcomes in elderly Hong Kong chinese aged 70 years and over.
Although increasing emphasis is being placed on strategies for successful aging, few studies have examined the relationship between lifestyle factors and mortality and other health outcomes in the old-old population. To examine the impact of physical activity, dietary habits, smoking, and alcohol consumption on 3-year mortality and other health outcomes. 2,032 Chinese subjects aged 70 years and older (mean age 80 years) were recruited territorywide by proportional random sampling and followed for 3 years. Baseline information was obtained by interview on level of physical activity, dietary habits (frequency of consumption per week of major food groups), alcohol consumption, and smoking habits. Outcome measures include mortality, self-perceived health status, frequency of hospitalization, geriatric depression score, and development of new diseases (stroke, heart disease, hypertension, diabetes mellitus, fractures). Logistic regression was used to examine the effects of lifestyle factors on each health outcome, with and without adjustment for age and baseline health status. The mortality risk is reduced with increasing physical activity, daily fish intake and moderate alcohol consumption, and avoidance of smoking; hospitalization is inversely associated with increasing activity; better self-perceived health is associated with moderate alcohol consumption and a non-smoking status, and there is an inverse relationship between depressive symptoms and increasing activity and moderate alcohol consumption. After adjustment for age and baseline health status, higher levels of physical activity are associated with decreased mortality and hospitalization; non-smokers have reduced mortality and a better self-perceived health, and moderate alcohol consumption is also associated with better self-perceived health. Lifestyle factors may influence health outcomes even in the old-old population.


[Recent developments of spoligotyping as applied to the study of epidemiology, biodiversity and molecular phylogeny of the Mycobacterium tuberculosis complex].
Spoligotyping (for 'spacer-oligonucleotide-typing'), a rapid method for genotyping of Mycobacterium tuberculosis complex using the principle of reverse hybridization, is based on the structure of the direct repeat (DR) locus. The DR locus is made up of a variable number of 36 bp DR repeats that are separated by unique inter-DR sequences of 35 to 41 bp. Fast and highly discriminatory, spoligotyping is an useful alternative to the IS6110-RFLP reference method for molecular typing of M. tuberculosis, in particular for isolates possessing five or few copies of IS6110. In this paper, we review the state of the art of spoligotyping through its main current applications. After a brief introduction to the principle of the technique and its description, we successively review recently published results concerning the molecular epidemiology of tuberculosis in humans and cattle, and discuss the main genotyping strategies currently in use to fingerprint the M. tuberculosis complex organisms. We also describe the recent applications of spoligotyping to study ancient DNA and report on recent developments of this technique to study the biodiversity of the M. tuberculosis complex, its contribution towards improved taxonomy and phylogenetics of the M. tuberculosis complex. Last but not least, potential applications of spoligotyping to study DNA recombination mechanisms are also discussed.


Microfluidic Single-Cell Analysis of Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes After Acute Myocardial Infarction.
Human induced pluripotent stem cells (iPSCs) are attractive candidates for therapeutic use, with the potential to replace deficient cells and to improve functional recovery in injury or disease settings. Here, we test the hypothesis that human iPSC-derived cardiomyocytes (iPSC-CMs) can secrete cytokines as a molecular basis to attenuate adverse cardiac remodeling after myocardial infarction. Human iPSCs were generated from skin fibroblasts and differentiated in vitro with a small molecule-based protocol. Troponin(+) iPSC-CMs were confirmed by immunohistochemistry, quantitative polymerase chain reaction, fluorescence-activated cell sorting, and electrophysiological measurements. Afterward, 2×10(6) iPSC-CMs derived from a cell line transduced with a vector expressing firefly luciferase and green fluorescent protein were transplanted into adult NOD/SCID mice with acute left anterior descending artery ligation. Control animals received PBS injection. Bioluminescence imaging showed limited engraftment on transplantation into ischemic myocardium. However, magnetic resonance imaging of animals transplanted with iPSC-CMs showed significant functional improvement and attenuated cardiac remodeling compared with PBS-treated control animals. To understand the underlying molecular mechanism, microfluidic single-cell profiling of harvested iPSC-CMs, laser capture microdissection of host myocardium, and in vitro ischemia stimulation were used to demonstrate that the iPSC-CMs could release significant levels of proangiogenic and antiapoptotic factors in the ischemic microenvironment. Transplantation of human iPSC-CMs into an acute mouse myocardial infarction model can improve left ventricular function and attenuate cardiac remodeling. Because of limited engraftment, most of the effects are possibly explained by paracrine activity of these cells.


Oral health behaviours amongst homeless people attending rehabilitation services in Ireland.
Research on oral health behaviours and dental care service uptake of drug users and those in recovery remains scant. The research aimed to explore and describe perspectives of drug users on their oral health behaviours, awareness of oral health complications caused by alcohol, cigarette and drug use, dental service uptake and opinions on improved dental service for active and recovering addicts. Two focus groups with a purposeful sample of participants (n = 15) were conducted in two treatment and rehabilitation settings. The semi-structured guide consisted of open questioning relating to dental access and uptake, oral health, awareness of oral cancers, nutrition and substance consumption on oral health, and opinions around optimum oral health and dental service provision for active drug users and those in recovery. Thematic analysis of narratives was conducted. Participants described barriers to access and uptake, poor levels of preventative dental care, DIY dentistry in the event of dental emergencies, substance use to self-medicate for dental pain, mixed awareness of the effects of sugary products and substance use on oral health and cancers, and emphasised the importance of preventative dental care and dental aesthetics when in recovery. Findings illustrate a profile of oral health behaviours in Irish drug users, with information useful for private and public practice, and in the further development of street, community and treatment setting oral health interventions.


Intimate partner violence and prescription of potentially addictive drugs: prospective cohort study of women in the Oslo Health Study.
To investigate the prescription of potentially addictive drugs, including analgesics and central nervous system depressants, to women who had experienced intimate partner violence (IPV). Prospective population-based cohort study. Information about IPV from the Oslo Health Study 2000/2001 was linked with prescription data from the Norwegian Prescription Database from 1 January 2004 through 31 December 2009. The study included 6081 women aged 30-60 years. Prescription rate ratios (RRs) for potentially addictive drugs derived from negative binomial models, adjusted for age, education, paid employment, marital status, chronic musculoskeletal pain, mental distress and sleep problems. Altogether 819 (13.5%) of 6081 women reported ever experiencing IPV: 454 (7.5%) comprised physical and/or sexual IPV and 365 (6.0%) psychological IPV alone. Prescription rates for potentially addictive drugs were clearly higher among women who had experienced IPV: crude RRs were 3.57 (95% CI 2.89 to 4.40) for physical/sexual IPV and 2.13 (95% CI 1.69 to 2.69) for psychological IPV alone. After full adjustment RRs were 1.83 (1.50 to 2.22) for physical/sexual IPV, and 1.97 (1.59 to 2.45) for psychological IPV alone. Prescription rates were increased both for potentially addictive analgesics and central nervous system depressants. Furthermore, women who reported IPV were more likely to receive potentially addictive drugs from multiple physicians. Women who had experienced IPV, including psychological violence alone, more often received prescriptions for potentially addictive drugs. Researchers and clinicians should address the possible adverse health and psychosocial impact of such prescription and focus on developing evidence-based healthcare for women who have experienced IPV.


Unique characteristics of the pyrrolysine system in the 7th order of methanogens: implications for the evolution of a genetic code expansion cassette.
Pyrrolysine (Pyl), the 22nd proteogenic amino acid, was restricted until recently to few organisms. Its translational use necessitates the presence of enzymes for synthesizing it from lysine, a dedicated amber stop codon suppressor tRNA, and a specific amino-acyl tRNA synthetase. The three genomes of the recently proposed Thermoplasmata-related 7th order of methanogens contain the complete genetic set for Pyl synthesis and its translational use. Here, we have analyzed the genomic features of the Pyl-coding system in these three genomes with those previously known from Bacteria and Archaea and analyzed the phylogeny of each component. This shows unique peculiarities, notably an amber tRNA(Pyl) with an imperfect anticodon stem and a shortened tRNA(Pyl) synthetase. Phylogenetic analysis indicates that a Pyl-coding system was present in the ancestor of the seventh order of methanogens and appears more closely related to Bacteria than to Methanosarcinaceae, suggesting the involvement of lateral gene transfer in the spreading of pyrrolysine between the two prokaryotic domains. We propose that the Pyl-coding system likely emerged once in Archaea, in a hydrogenotrophic and methanol-H2-dependent methylotrophic methanogen. The close relationship between methanogenesis and the Pyl system provides a possible example of expansion of a still evolving genetic code, shaped by metabolic requirements.


CT and MRI imaging diagnosis of epidural idiopathic sterile pyogranulomatous inflammation in a dog spinal canal.
A 12-year-old neutered male shih tzu developed progressive pelvic limb paraparesis. Computed tomography showed a radiolucent mass lesion in the spinal canal at the left side of the 11th thoracic vertebra. The mass was not enhanced by intravenous contrast medium injection. It was hyperintense on both T1- and T2-weighted magnetic resonance images. The signal intensity of the mass was decreased with a fat suppression technique, indicating a fatty origin. After removal of the mass via T11-T12 hemilaminectomy, chronic panniculitis was confirmed by histopathological examination. This case demonstrates the utility of computed tomography and magnetic resonance imaging for the diagnosis of spinal canal pyogranulomatous inflammation.